BACKGROUND: Tumor shrinkage by preoperative radiochemotherapy (RCT) can markedly improve surgery in locally advanced (T4) rectal cancer with clear resection margins and may enable sphincter preservation in low-lying tumors. However, tumor response varies considerably, even among tumors treated according to the same protocol. If one is able to identify patients with highly radio-responsive tumors at the time of diagnosis, a selective and individualized policy of preoperative RCT might be pursued. METHODS: The apoptotic index (AI), Ki-67, p53, and bcl-2 were evaluated by immunohistochemistry on pretreatment biopsies from 44 patients treated uniformly according to a prospective neoadjuvant RCT protocol (CAO/AIO/ARO-94). Treatment response was assessed histopathologically in the resected surgical specimen, using a five-point grading system. Expression of each marker was correlated with tumor response and relapse-free survival after curative surgery. RESULTS: Tumors with complete (n = 3) or good (n = 28) response to RCT showed significantly higher pretreatment levels of apoptosis (mean AI: 2.06%) than tumors with moderate (n = 7), minimal (n = 5), or no regression (n = 1) from RCT (AI: 1.44%, p = 0.003). The AI was significantly related to Ki-67 (p = 0.05), but not to p53 and bcl-2 status. Tumor regression and AI best predicted relapse-free survival after combined modality treatment and curative surgery. CONCLUSION: Spontaneous apoptosis in rectal cancer may serve as an important predictor of tumor regression from RCT in rectal cancer and as a significant prognosticator of relapse-free survival. Thus, this molecular marker may finally help to tailor therapy with regard to (neo-) adjuvant treatment of rectal cancer.
BACKGROUND:Tumor shrinkage by preoperative radiochemotherapy (RCT) can markedly improve surgery in locally advanced (T4) rectal cancer with clear resection margins and may enable sphincter preservation in low-lying tumors. However, tumor response varies considerably, even among tumors treated according to the same protocol. If one is able to identify patients with highly radio-responsive tumors at the time of diagnosis, a selective and individualized policy of preoperative RCT might be pursued. METHODS: The apoptotic index (AI), Ki-67, p53, and bcl-2 were evaluated by immunohistochemistry on pretreatment biopsies from 44 patients treated uniformly according to a prospective neoadjuvant RCT protocol (CAO/AIO/ARO-94). Treatment response was assessed histopathologically in the resected surgical specimen, using a five-point grading system. Expression of each marker was correlated with tumor response and relapse-free survival after curative surgery. RESULTS:Tumors with complete (n = 3) or good (n = 28) response to RCT showed significantly higher pretreatment levels of apoptosis (mean AI: 2.06%) than tumors with moderate (n = 7), minimal (n = 5), or no regression (n = 1) from RCT (AI: 1.44%, p = 0.003). The AI was significantly related to Ki-67 (p = 0.05), but not to p53 and bcl-2 status. Tumor regression and AI best predicted relapse-free survival after combined modality treatment and curative surgery. CONCLUSION: Spontaneous apoptosis in rectal cancer may serve as an important predictor of tumor regression from RCT in rectal cancer and as a significant prognosticator of relapse-free survival. Thus, this molecular marker may finally help to tailor therapy with regard to (neo-) adjuvant treatment of rectal cancer.
Authors: S E Baldus; S P Mönig; W Schröder; R Metzger; S Lang; T K Zirbes; J Thiele; R P Müller; H P Dienes; A H Hölscher; P M Schneider Journal: Pathologe Date: 2004-11 Impact factor: 1.011
Authors: Andrea Ambrosini-Spaltro; Fabrizio Salvi; Christine M Betts; Giovanni P Frezza; Antonio Piemontese; Pietro Del Prete; Cristina Baldoni; Maria P Foschini; Giuseppe Viale Journal: Virchows Arch Date: 2005-12-20 Impact factor: 4.064
Authors: Dermot T McDowell; Fraser M Smith; John V Reynolds; Stephen G Maher; Collette Adida; Paul Crotty; Eoin F Gaffney; Donal Hollywood; Brian Mehigan; Richard B Stephens; M J Kennedy Journal: Int J Colorectal Dis Date: 2009-07-11 Impact factor: 2.571
Authors: M J E M Gosens; R C Dresen; H J T Rutten; G A P Nieuwenhuijzen; J A W M van der Laak; H Martijn; I Tan-Go; I D Nagtegaal; A J C van den Brule; J H J M van Krieken Journal: Ann Oncol Date: 2008-07-29 Impact factor: 32.976
Authors: M Kikuchi; T Mikami; T Sato; W Tokuyama; K Araki; M Watanabe; K Saigenji; I Okayasu Journal: Br J Cancer Date: 2009-06-02 Impact factor: 7.640